Noon conference mgus

1. Noon Conference
Marcus Lacey

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MGUS/MM
MGUS Definition
Distinct Types
MGUS Further Work Up
Disease Course and Monitoring
MM Review
MM Renal Disease
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MGUS Definition/Prevalence
Asymptomatic premalignant clonal plasma cell or
lymphoplasmacytic proliferative disorder
• M protein at concentration <3 g/dL
• Bone marrow with <10% monoclonal plasma cells
• Absence of end-organ damage
• Present in >3% of Caucasian population over 50y
• Typically dx on protein electrophoresis in evaluation
of unrelated symptoms
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3 Distinct types
Non IgM MGUS:
• Most common
• Can progress to MM, or AL amyloid or light chain
deposition disease (LCDD)
• IgG type has lower risk of progression
IgM MGUS:
• 15%
• Progresses to Waldenstrom’s Macroglobulinemia
Light Chain MGUS:
• Rare
• Progresses to light chain MM, AL Amyloid or LCDD
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Further Work Up
To demonstrate no end organ damage, <3 g/dL M protein and <10% in BM
• CBC
• Serum Calcium, Creatinine
• SPEP/UPEP
• Free Light Chain Assay
• Quantitation of immunoglobulins
• Skeletal Survey
• Unless low risk MGUS – IgM type or IgG with nl. FLC ratio
• A bone marrow biopsy
• M-protein ≥1.5 g/dL
• IgA MGUS of any size
• abnormal serum FLC ratio
• any abnormalities of the complete blood count, creatinine, calcium,
or bone survey
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Disease Course and Monitoring
Progress to advance disease at rate of 1% per year
Median survival is only slightly lower than controls
Monitoring:
• Pts w/ low risk IgG type, M protein <1.5 and nl FLC ratio
• Annual hx and physical only
• Rate of progression 5% at 20yrs
• All other patients
• Annual SPEP, serum FLC assay, complete blood count,
creatinine, and serum calcium
• Encourage to seek medical care for new sxs
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Are there known complications of MGUS?
1. Yes, Anemia and fractures
2. No complications
3. Yes, Fractures and Thrombosis
4. Yes, Peripheral Neuropathy, Fx, and Thrombosis
5. Yes, Anemia, Fx, and Thombosis
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Complications
Monoclonal Gammopathy of Clinical Sig.
• MGUS w organ damage related to immunoglobulin
• Renal disease and/or neuropathy
• Weigh risk/benefit of treatment
Fracture:
• Higher risk in axial skeleton
• DEXA scan, optimize Ca/Vit D
• Bisphosphonates if osteoporosis
Thromboembolic disease
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Review of the Case
Multiple Myeloma Presentation
• Fatigue and Weight Loss
• Anemia normochromic/normocytic
• Bone pain often in back or chest (plasmacytomas)
• Neurologic Disease – cord compression and/or
neuropathy
• Infection
• Renal Disease
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Renal Disease in MM
Renal Failure is often presenting sign
Most commonly Light chain cast nephropathy or
Hypercalcemia
• SPEP/UPEP – if light chains are present pts are at risk
• Bx may not be necessary:Light chain assay – >1500
(our pt: 1980) cast nephropathy is presumed dx.
• UA protein and Urine protein disassociation
Less common causes: AL amyloid, LC deposition disease
• Albuminuria
• Less likely to cause severe kidney injury
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What is nephrotic range proteinuria
1. 1.5 g/day
2. 3.5g/day
3. 4.5g/day
4. 5g/day
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Renal US
What are potential findings?
What is medical renal disease?
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Urinalysis Findings
What would you see in ANCA Vasculitis?
What would you see in Interstitial Nephritis?
Rhabdomyolysis?
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Illness Scripts
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Multiple Myeloma
Pathophysiology
Malignant Clonal Plasma Cell Proliferation, genetic defects: Hyperploidy or
translocations
Epidemiology
There is a genetic component, older age (>50), Immunosupression,
Environmental Exposure and M>F
Time course Variable
Clinical presentation
• Generalized weakness and/or weight loss
• Anemia normochromic/normocytic
• Bone pain often in back or chest (plasmacytomas)
• Neurologic Disease – cord compression and/or neuropathy
• Infection
• Renal Disease
Diagnostics
Labs: SPEP/UPEP, Free Light Chain Assay, Immunoglobulin Levels, CMR,
CBC w Diff, Peripheral Smear, LDH, CRP
Other testing: Bone Marrow Bx, Renal US, CT c/a/p
Specimen: UA, 24 hr urine protein collection, Urine p/c ratio
Therapeutics
HCT for those eligible with 3-4 mo of induction therapy with Bortezomib
based triplet regimen of chemo followe by stem cell collection and
autologous transplant. 2 years of maintenance therapy thereafter

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References
• Kyle RA, Gertz MA, Witzig TE, et al. Review of 1027 patients with newly
diagnosed multiple myeloma. Mayo Clin Proc 2003; 78:21.
• Smith A, Wisloff F, Samson D, et al. Guidelines on the diagnosis and
management of multiple myeloma 2005. Br J Haematol 2006; 132:410.
• Dimopoulos M, Kyle R, Fermand JP, et al. Consensus recommendations
for standard investigative workup: report of the International Myeloma
Workshop Consensus Panel 3. Blood 2011; 117:4701.
• Kyrtsonis MC, Vassilakopoulos TP, Kafasi N, et al. Prognostic value of
serum free light chain ratio at diagnosis in multiple myeloma. Br J
Haematol 2007; 137:240.
• Rajkumar SV, Dimopoulos MA, Palumbo A, et al. International Myeloma
Working Group updated criteria for the diagnosis of multiple myeloma.
Lancet Oncol 2014; 15:e538.
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